None listed
Conditions
Brief summary
The small intestine is the key interface between ingested food and the human body, particularly given its capacity to “sense” the presence of nutrients in much the same way as the tongue, through activation of similar taste receptors. This taste perception can influence nutrient uptake, as well as the release of gut hormones and neurotransmitters involved in the regulation of gastrointestinal motility, energy intake and blood glucose homeostasis. The purpose of the study is to provide proof of concept that intestinal bitter taste sensing has a favourable effect on metabolic control. Specifically, the study will evaluate the hypothesis that activation of intestinal bitter taste receptors (by intraduodenal administration of a bitter chemical, denatonium benzoate) augments secretion of gut hormones, thereby increasing insulin, suppressing glucagon and ghrelin, and modulating antropyloroduodenal motility (to slow gastric emptying), with a consequent reduction of the blood glucose response to small intestinal glucose infusion and potentiation of the reduction in energy intake in healthy human participants.
Interventions
Following enrolment, each subject will be studied on three occasions, separated by at least 7 days, in a double-blind, randomized fashion. On each study day, following correct positioning of the intraduodenal catheter, intraduodenal infusion of (i) low dose (10 mg dissolved in 250 mL water) or (ii) high dose (30 mg dissolved in 250 mL water) of denatonium benzoate or (iii) control (250 mL water only) will be commenced, with 100 mL infused during t = -60 to 0 min, and the remaining 150 mL infuse
Following enrolment, each subject will be studied on three occasions, separated by at least 7 days, in a double-blind, randomized fashion. On each study day, following correct positioning of the intraduodenal catheter, intraduodenal infusion of (i) low dose (10 mg dissolved in 250 mL water) or (ii) high dose (30 mg dissolved in 250 mL water) of denatonium benzoate or (iii) control (250 mL water only) will be commenced, with 100 mL infused during t = -60 to 0 min, and the remaining 150 mL infused over the next 90 min (t = 0 to 90 min). All doses are administered at study site by staff. During the latter period (t = 0 to 90 min), ID glucose will be infused at 2 kcal/min. At the end of infusions, a cold buffet meal will be given for evaluation of energy intake (t = 90-120 min).
Sponsors
Royal Adelaide Hospital
Study design
Allocation
Randomised controlled trial
Intervention model
Crossover
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
All
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male and females aged 18 – 55 years * Body mass index (BMI) 19 - 25 kg/m2 * Haemoglobin above the lower limit of the normal range (ie. >135g/L for men and 115g/L for women), and ferritin above the lower limit of normal (ie. >30ng/mL for men and >20mg/mL for women)
Exclusion criteria
* Use of any medication that may influence gastrointestinal motor function, body weight or appetite (e.g. antihypertensive drugs, domperidone and cisapride, anticholinergic drugs (e.g. atropine), metoclopramide, erythromycin, hyoscine, orlistat, green tea extracts, Astragalus, St. John's Wort etc.) * Evidence of drug abuse, consumption of more than 20 g alcohol or 10 cigarettes on a daily basis * History of gastrointestinal disease, including significant upper or lower gastrointestinal symptoms, pancreatitis, or previous gastrointestinal surgery (other than uncomplicated appendicectomy or cholecystectomy) * Other significant illness, including epilepsy, cardiovascular or respiratory disease * Impaired renal or liver function (as assessed by calculated creatinine clearance < 90 mL/min or abnormal liver function tests (> 2 times upper limit of normal range)) * Donation of blood within the previous 3 months * Participation in any other research studies within the previous 3 months * Inability to give informed consent * Female participants who are pregnant or planning for pregnancy, or are lactating * Vegetarians
Outcome results
None listed